Effects of charybdotoxin and iberiotoxin on the spontaneous motility and tonus of different guinea pig smooth muscle tissues.

Charybdotoxin (ChTX) and iberiotoxin (IbTX), two potent peptidyl blockers of the high conductance Ca(2+)-activated K+ channel (PK,Ca) were used to probe the role of this channel in regulating the contractility of various smooth muscles isolated from the guinea pig. Of the spontaneously contracting tissues that have been investigated, bladder and taenia coli are affected by ChTX, whereas portal vein and uterus are relatively insensitive. In the former two tissues, ChTX (10-100 nM) produces a concentration-dependent increase in contractility, with bladder being most sensitive to action of the toxin. ChTX also causes a contracture of quiescent aortic rings, although not affecting indomethacin-treated trachea. In order to demonstrate that the effects of ChTX are due specifically to blockage of PK,Ca, rather than to inhibition of some other K+ channel, two other inhibitors of PK,Ca were monitored. IbTX (10-100 nM), a selective inhibitor of PK,Ca, and tetraethylammonium ion, which blocks PK,Ca at low (0.1-3 mM) concentrations, both increase the myogenic activity of bladder, but not portal vein. In addition, IbTX causes a sustained contracture of aorta. Taken together, these data indicate that the increased contractility of certain guinea pig smooth muscles produced by ChTX, IbTX and tetraethylammonium ion is the result of selective inhibition of PK,Ca. It is suggested that in spontaneously active bladder and taenia coli, PK,Ca provides a repolarization pathway after tissue depolarization, whereas in quiescent aorta, PK,Ca maintains cellular resting potential. In contrast, in indomethacin-treated trachealis muscle, ChTX-sensitive K+ channel pathways are not involved in controlling resting tension.(ABSTRACT TRUNCATED AT 250 WORDS)